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In the current setting of organ shortage, brain-dead liver donors with recent liver trauma (RLT) represent a potential pool of donors. Yet, data on feasibility and safety of liver transplantation (LT) using grafts with RLT are lacking.All liver grafts from brain-dead donors with RLT proposed for LT between 2010 and 2018 were identified from the nationwide CRISTAL registry of the Biomedicine Agency. The current study aimed at evaluating 1-y survival as the primary endpoint.Among 11 073 LTs, 142 LTs (1.3%) using grafts with RLT were performed. These 142 LTs, including 23 split LTs, were performed from 131 donors (46.1%) of 284 donors with RLT proposed for LT. Transplanted grafts were procured from donors with lower liver enzymes levels (P 0.001) and less advanced liver trauma according to the American Association for the Surgery of Trauma liver grading system (P 0.001) compared with not transplanted grafts. Before allocation procedures, 20 (7%) of 284 donors underwent damage control intervention. During transplantation, specific liver trauma management was needed in 19 patients (13%), consisting of local hemostatic control (n = 15), partial hepatic resection on back-table (n = 3), or perihepatic packing (n = 1). Ninety-day mortality and severe morbidity rates were 8.5% (n = 12) and 29.5% (n = 42), respectively. One-year overall and graft survival rates were 85% and 81%, and corresponding 5-y rates were 77% and 72%, respectively.Using liver grafts from donors with RLT seems safe with acceptable long-term outcomes. All brain-dead patients with multiorgan trauma, including liver injury, should be considered for organ allocation.

Liver transplantation (LT) is the treatment of end-stage non-alcoholic liver disease (NAFLD), that is decompensated cirrhosis and/or complicated by hepatocellular carcinoma (HCC). Few data on long-term outcome are available. The aim of this study was to evaluate overall patient and graft survivals and associated predictive factors.This retrospective multicentre study included adult transplant patients for NAFLD cirrhosis between 2000 and 2019 in participating French-speaking centres.A total of 361 patients (69.8% of male) were included in 20 centres. The median age at LT was 62.3 years [57.4-65.9] and the median MELD score was 13.9 [9.1-21.3]; 51.8% of patients had HCC on liver explant. Between 2004 and 2018, the number of LT for NAFLD cirrhosis increased by 720%. A quarter of the patients had cardiovascular history before LT. Median follow-up after LT was 39.1 months [15.8-72.3]. Patient survival at 1, 5 and 10 years after LT was 89.3%, 79.8% and 68.1% respectively. The main causes of death were sepsis (37.5%), malignancies (29.2%) and cardiovascular events (22.2%). In multivariate analysis, three risk factors for overall mortality after LT were recipient pre-LT BMI 32 kg/mSurvival after LT for NAFLD cirrhosis is good at 5 years. Donor and recipient age, and cardiovascular history, are major prognostic factors to consider.

Background: Anastomotic biliary stricture (ABS) remains the most frequent complication after liver transplantation (LT). This study aimed to identify new anastomotic biliary stricture risk factors, with a specific focus on postoperative events. Additionally, ABS management and impact on patient and graft survival were assessed.Methods: All consecutive patients who underwent LT with duct-to-duct anastomosis between 2010 and 2019 were included. All patients who died within 90 days after LT due to non-ABS-related causes were excluded.Results: Among 240 patients, 65 (27.1%) developed ABS after a median time of 142 days (range, 13–1265). Median follow-up was 49 months (7–126). Upon multivariable analysis, donor BMI (OR=0.509, p = 0.037), post-LT CMV primoinfection (OR = 5.244, p < 0.001) or reactivation (OR = 2.421, p = 0.015) and the occurrence of post-LT anastomotic biliary fistula (OR = 2.691, p = 0.021) were associated with ABS. Anastomotic technical difficulty did not independently impact the risk of ABS (OR = 1.923, p = 0.051). First-line ABS treatment was systematically endoscopic (100%), and required a median of 2 (range, 1–11) procedures per patient. Repeat LT was not required in patients developing ABS. The occurrence of ABS was not associated with overall patient survival (p = 0.912) nor graft survival (p = 0.521).Conclusion: The risk of developing ABS after LT seems driven by the occurrence of postoperative events such as CMV infection and anastomotic fistula. In this regard, the role of CMV prophylaxis warrants further investigations.

Liver tumors are common and may be unamenable to surgery or ablative treatments. Consequently, other treatments have been devised. To assess the safety and efficacy of transarterial radioembolization (TARE) with Yttrium-90 for hepatocellular carcinoma (HCC), liver-dominant hepatic colorectal cancer metastases (mCRC), and cholangiocarcinoma (CCA), performed according to current recommendations, we conducted a single-center retrospective study in 70 patients treated with TARE (HCC, n = 44; mCRC, n = 20; CCA, n = 6). Safety and toxicity were assessed using the National Cancer Institute Common Terminology Criteria. Treatment response was evaluated every 3 months on imaging studies using Response Evaluation Criteria in Solid Tumors (RECIST) or mRECIST criteria. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. The median delivered dose was 1.6 GBq, with SIR-Spheres® or TheraSphere® microspheres. TARE-related grade 3 adverse events affected 17.1% of patients. Median follow-up was 32.1 months. Median progression-free survival was 5.6 months and median overall time from TARE to death was 16.1 months and was significantly shorter in men. Progression-free survival was significantly longer in women (HR, 0.49; 95%CI, 0.26–0.90; p = 0.031). Risk of death or progression increased with the number of systemic chemotherapy lines. TARE can be safe and effective in patients with intermediate- or advanced-stage HCC, CCA, or mCRC refractory or intolerant to appropriate treatments.

International audience; Background: After liver transplantation (LT),de novo malignancies are one of the leading causes of late mortality. The aim of the present retrospective study was to identify the risk factors of de novo malignancies in a large cohort of LT recipients in France, using Fine and Gray competing risks regression analysis.Methods: The study population consisted in 11004 adults transplanted between 2000 and 2013, who had no history of pre-transplant malignancy, except primary liver tumor. A Cox model adapted to the identification of prognostic factors (competitive risks) was used.Results: From the entire cohort, one (or more)de novo malignancy was reported in 1480 L T recipients (13.45%). The probability to develop a de novo malignancy after LT was 2.07% at 1 year, 13.30% at 5 years, and 28.01% at 10 years. Of the known reported malignancies, the most common malignancies were hematological malignancy (22.36%), non-melanoma skin cancer (19.53%) and lung cancer (12.36%). According to Fine and Gray competing risks regression multivariate analysis, were significant risk factors for post-LT de novo malignancy: recipient age (Subdistribution Hazard Ratio (SHR) = 1.03 95%CI 1.03-1.04), male gender (SHR = 1.45 95%CI 1.27-1.67), non-living donor (SHR = 1.67 95%CI 1.14-2.38), a first LT (SHR = 1.35 95%CI 1.09-1.69) and the type of initial liver disease (alcohol-related liver disease (SHR = 1.63 95%CI 1.22-2.17), primary sclerosing cholangitis (SHR = 1.98 95%CI 1.34-2.91), and primary liver tumor (SHR = 1.88 95%CI 1.41-2.54)). Initial immunosuppressive regimen had no significant impact.Conclusion: The present study confirms that LT recipient characteristics are associated with the risk ofde novo malignancy and this underlines the need for personalized screening in order to improve survival.

Background & Aims Reinforced hepatocellular carcinoma (HCC) surveillance using magnetic resonance imaging (MRI) could increase early tumour detection but faces cost-effectiveness issues. In this study, we aimed to evaluate the cost-effectiveness of MRI for the detection of very early HCC (Barcelona Clinic Liver Cancer [BCLC] 0) in patients with an annual HCC risk >3%. Methods French patients with compensated cirrhosis included in 4 multicentre prospective cohorts were considered. A scoring system was constructed to identify patients with an annual risk >3%. Using a Markov model, the economic evaluation estimated the costs and life years (LYs) gained with MRI vs. ultrasound (US) monitoring over a 20-year period. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the incremental costs by the incremental LYs. Results Among 2,513 patients with non-viral causes of cirrhosis (n = 840) and/or cured HCV (n = 1,489)/controlled HBV infection (n = 184), 206 cases of HCC were detected after a 37-month follow-up. When applied to training (n = 1,658) and validation (n = 855) sets, the construction of a scoring system identified 33.4% and 37.5% of patients with an annual HCC risk >3% (3-year C-Indexes 75 and 76, respectively). In patients with a 3% annual risk, the incremental LY gained with MRI was 0.4 for an additional cost of €6,134, resulting in an ICER of €15,447 per LY. Compared to US monitoring, MRI detected 5x more BCLC 0 HCC. The deterministic sensitivity analysis confirmed the impact of HCC incidence. At a willingness to pay of €50,000/LY, MRI screening had a 100% probability of being cost-effective. Conclusions In the era of HCV eradication/HBV control, patients with annual HCC risk >3% represent one-third of French patients with cirrhosis. MRI is cost-effective in this population and could favour early HCC detection. Lay summary The early identification of hepatocellular carcinoma in patients with cirrhosis is important to improve patient outcomes. Magnetic resonance imaging could increase early tumour detection but is more expensive and less accessible than ultrasound (the standard modality for surveillance). Herein, using a simple score, we identified a subgroup of patients with cirrhosis (accounting for >one-third), who were at increased risk of hepatocellular carcinoma and for whom the increased expense of magnetic resonance imaging would be justified by the potential improvement in outcomes., Graphical abstract, Highlights • HCC risk stratification in patients with cirrhosis aims at improving performance of cancer surveillance. • Using a simple scoring system, one-third of patients with cirrhosis with an annual HCC risk >3% can be easily identified. • Semi-annual surveillance using MRI in this population could enable the cost-effective detection of 5x more BCLC 0 HCCs.

International audience; Objective Malnutrition impairs prognosis in liver cirrhosis. Our aims were to determine (1) if transversal (TPTI) and axial (APTI) psoas thickness indices predict mortality in cirrhotic patients and (2) the feasibility and reproducibility of transversal (TDPM) and axial (ADPM) diameters of the psoas muscle measurements.Methods This was a retrospective study. Inclusion criteria included cirrhosis diagnosis, on liver transplantation waiting list, and abdominal computed tomography (CT) scan within the 3 mo preceding list inscription. TDPM and ADPM were measured on a single umbilicus-targeted CT image by non-expert and expert operators. TPTI or APTI (mm/m) were calculated as TDPM or ADPM/height (m). Area under the receiver operating characteristic curve (AUC) and Cox proportional hazard models were assessed. TPTI and APTI interobserver agreement κ correlation test.Results A total of 173 patients were included. Low TPTI was associated with increased mortality AUC = 0.66 (95% confidence interval, 0.51–0.80). TPTI was the only factor associated with mortality (hazard ratio = 0.87, 95% confidence interval 0.76–0.99, P = 0.034). There was an almost perfect interobserver agreement between the two operators TDPM, κ = 0.97; ADPM, κ = 0.94; P < 0.0001.Conclusions TPTI measured on umbilicus-targeted CT scan before inscription on the waiting list for liver transplantation predicts mortality of cirrhotic patients. TPTI measurement is easy and reliable, even by a non-trained operator, and this is highly feasible in daily clinical practice.

Etat de la question Les progres en transplantation hepatique et les changements epidemiologiques recents ont conduit a une augmentation du nombre de receveurs âges de plus de 65 ans, et ce malgre un contexte de penurie d’organes. Nous avons etudie l’impact de l’âge avance des receveurs sur la mortalite a cinq et dix ans d’une transplantation hepatique. Materiel et methodes Les patients majeurs transplantes pour la premiere fois entre 2007 et 2017, enregistres dans la base nationale de l’Agence de la biomedecine francaise etaient inclus. Des modeles flexibles de survie observee et de survie nette ont ete utilises pour tenir compte des effets dependants du temps et/ou non log-lineaires et de la mortalite attendue pour chaque patient compte tenu de son sexe et de son âge. Resultats Au total, 7610 patients ont ete inclus (âge moyen a la greffe de 55 ans [± 10,5]). Plus les receveurs etaient âges, meilleure etait leur fonction hepatique. Les analyses de survie observee comme de survie nette ont montre une association significative entre l’augmentation de l’âge du receveur et le risque de deces. Cependant si cet effet pejoratif etait majeur dans la premiere annee suivant la greffe, il diminuait progressivement au cours du suivi. Une difference absolue de 8 % (50 % versus 42 %) de survie nette persiste malgre tout a 10 ans entre des receveurs de 28 et 71 ans. Conclusion Malgre une selection des candidats âges, l’âge a la greffe etait associe a une augmentation du risque de deces, particulierement marquee dans la premiere annee suivant la transplantation. Cet effet diminuait ensuite mais restait present a cinq et dix ans de la greffe, y compris apres prise en compte de la mortalite attendue par âge et par sexe dans la population francaise.

International audience

International audience; BACKGROUND AND AIMS: In many countries, current treatment for patients with chronic hepatitis C involves a combination of peginterferon and ribavirin, associated with a protease inhibitor for hepatitis C virus genotype 1. More recent and efficient less toxic antiviral treatments are now available for some patients. Thus, the decision to treat or to wait is challenging. The aims of this study were to: (a) estimate the proportion of treated patients, (b) evaluate the reasons for this decision, and (c) examine the patients' points-of-view in treatment decision. METHODS: This was a prospective study conducted at three French referral centers between March and June 2013. Epidemiological and virological data, reasons for treatment or nontreatment, and data on the doctors' and patients' choices were collected. RESULTS: A total of 255 patients were analyzed. Only 52.6% of patients with fibrosis of 2 or higher were treated. Treatment uptake was reduced in the following groups: previously treated patients, those with poor tolerance during prior treatment, those with heavy alcohol consumption, and those with hepatocellular carcinoma. Of the cirrhotic patients, 55% were not treated: 51.1% had a contraindication, 22.2% had a previous nonresponse. When treatment was refused by the patient, fear of side effects and professional problems were the most frequently cited reasons (90 and 40%, respectively). CONCLUSION: Patients were treated primarily according to consensus guidelines. However, only 45% of cirrhotic patients were treated. In 7.6% of the cases, the patient refused therapy. This study enabled us to measure the importance of patient choice in medical decision-making. Well-informed patients expected not only more efficient but also well-tolerated therapy

The role of endotoxemia related to intestinal bacterial translocation in worsening liver disease is the subject of many studies, but its impact on cirrhosis mortality has not been well evaluated. In this study, 3-hydroxymyristate (3-HM) (specific lipid of lipopolysaccharides) was directly quantified by an innovative patented assay with the aim of assessing the impact on cirrhosis mortality. The 3-HM concentration was measured in 593 patients with alcoholic or viral cirrhosis in stable clinical condition. A Cox hazards regression model was used to evaluate association between 3-HM and its fractions bound or nor bound to lipoprotein and the mortality. The 3-HM concentration was increased in patients with more severe cirrhosis (p

International audience; PURPOSE: Sorafenib is the standard of care for advanced hepatocellular carcinoma (HCC). The peak incidence of HCC is around 70 years. We aimed to evaluate safety and efficacy of sorafenib in the elderly population. METHODS: We retrospectively reviewed data from patients treated with sorafenib for HCC at our institution. We compared safety and efficacy data across different age groups. RESULTS: Since 2005, 129 patients were treated, 78 (60.5 %) were \textless70 years old and 51 (39.5 %) were ≥70. The frequency of dose reduction was similar between the two groups (48.7 vs. 58.8 %), as was the occurrence of severe toxicities (41.0 vs. 51.0 %) and hospitalization due to toxicity (9.0 vs. 13.7 %). However, asthenia and bleeding were more frequent in the elderly. The higher frequency of bleeding was explained by concomitant antiplatelet treatments, and major asthenia was frequent in PS1 elderly patients. There was a trend toward less frequent interruption of treatment in the younger group (25.6 vs. 39.2 %) and significantly less frequent definitive discontinuation of treatment due to toxicity (24.4 vs. 45.1 %). Median progression-free survival was 5.6 months in both age groups, while median overall survival was 9.6 months in the younger age group and 12.6 months in the older age group. CONCLUSION: Sorafenib showed similar results in terms of safety and efficacy in the elderly and younger HCC populations. Careful baseline evaluation is needed for patient's selection in the elderly population, including discussion about antiplatelet therapy discontinuation and caution in PS1 patients, as well as active management of toxicity.

To assess the efficacy and the safety of GlubranA retrospective review of consecutive patients who underwent emergent NBCA-MS Glubran104 patients underwent technically successful embolization with bleeding located in muscles (n = 34, 32.7%), digestive tract (n = 28, 26.9%), and viscera (n = 42, 40.4%). Clinical success rate was 76% (n = 79) and 30-day mortality rate was 21.2% (n = 22). Clinical failure was significantly associated with mortality (p 0.0001). A number of RBC units transfused greater than or equal to 3 were associated with poorer clinical success (p = 0.025) and higher mortality (p = 0.03). Complications (n = 4, 3.8%) requiring surgery occurred only at puncture site. No ischemic complications requiring further invasive treatment occurred. Mean TAE treatment time was 4.55 min.NBCA-MS Glubran

Background: Defects in human hemochromatosis protein (HFE) cause iron overload due to reduced hepatic hepcidin secretion. Liver transplantation (LT) is a key treatment for potential complications from HFE- related hereditary hemochromatosis (HH). This study evaluated hepcidin secretion and iron burden after LT to elucidate HH pathophysiology. Methods: Patients (n=18) homozygous for the p.Cys282Tyr mutation in the HFE gene underwent LT between 1999 and 2008. Serum iron, serum hepcidin, and hepatic iron concentrations were determined before LT and at the end of follow-up (median 57 months). Mortality and causes of death were determined. Survival was compared to that of the overall patient population that received LT. Results: Before LT, serum hepcidin levels were low (0.54 ± 2.5 nmol/L; normal range: 4-30 nmol/L). After LT, 11 patients had iron evaluations; none received iron depletion therapy; all had normal transferrin saturation. The mean serum ferritin was 185 (±99) µg/L. Magnetic resonance imaging showed that iron overload was absent in 9 patients, mild in one patient with metabolic syndrome, and high (180 µmol/g) in one patient with hereditary spherocytosis unmasked after liver transplantation. At the end of follow-up, serum hepcidin was normal in 10 patients (11.12 ± 7.6 nmol/L; p

Etat de la question Le role de l’endotoxemie liee a la translocation bacterienne sur l’aggravation de la cirrhose fait l’objet de nombreuses etudes, mais son impact sur la mortalite au cours de la cirrhose est mal connu. Le but de ce travail etait d’etudier l’impact de la concentration sanguine de 3-hydroxymyristate (3-HM) total (composant specifique des lipopolysaccharides, endotoxine), sur le risque de deces et de complications des malades cirrhotiques. Materiel et methodes Au total, 593 patients atteints de cirrhose alcoolique ou virale, sans carcinome hepatocellulaire ont ete inclus entre 2008 et 2012 dans six centres hospitalo-universitaires francais. Le dosage de 3-HM total, libre et lie aux lipoproteines a ete realise en l’absence de complication aigue de la cirrhose par une methode innovante et brevetee de dosage massique des LPS. Le suivi annuel pendant cinq ans a permis de relever la survenue de complications ou du deces. L’analyse de survie a ete realisee par un modele de Cox multivarie avec stratification sur le centre et la severite de la cirrhose. Resultats Les patients avec une concentration de 3-HM elevee avait une cirrhose plus severe que les autres selon les scores de Child-Pugh et de Meld (p Conclusion Une concentration elevee de 3-HM, marqueur specifique de l’endotoxemie, est associee a un sur-risque de deces a cinq ans chez les patients avec cirrhose alcoolique ou virale compensee (Child Pugh A) suggerant un role majeur de la translocation bacterienne dans l’aggravation de la cirrhose.

Las enfermedades por sobrecarga de hierro en los ninos abarcan un amplio abanico de enfermedades geneticas y adquiridas. La identificacion de las causas geneticas ha sido relativamente reciente, a raiz del descubrimiento del gen HFE. Se ha observado que, ademas de la hemocromatosis de tipo 1 (vinculada al gen HFE), que se manifiesta en la edad adulta, varias formas de sobrecarga de hierro que afectaban a pacientes jovenes se debian a mutaciones de genes no relacionados con HFE. Se trata de enfermedades poco comunes pero que, a diferencia de la hemocromatosis vinculada al gen HFE, no afectan unicamente a pacientes caucasicos. El exceso de hierro esta relacionado, como en la hemocromatosis de tipo 1, con una hipohepcidinemia que aumenta la absorcion digestiva de hierro. Entre las causas adquiridas, predominan las sobrecargas de hierro que se desarrollan en el contexto de diversos trastornos hematologicos y estan relacionadas no solo con la transfusion de hierro, sino tambien con un exceso de absorcion digestiva de este, debido a hipohepcidinemia por diseritropoyesis. Desde el punto de vista diagnostico, estas diversas enfermedades se han beneficiado en gran medida de la resonancia magnetica (RM), para cuantificar de forma no invasiva la carga de hierro visceral, asi como de los avances de la genetica molecular, para identificar las mutaciones implicadas. Desde el punto de vista terapeutico, la deplecion mediante sangrias es el tratamiento de primera linea de las sobrecargas geneticas. La quelacion oral se ha convertido en el tratamiento de eleccion para las sobrecargas transfusionales. Con la condicion de que se instauren de forma precoz, estos enfoques terapeuticos permiten no solo transformar el pronostico vital, sino mejorar sensiblemente la calidad de vida de estos jovenes pacientes.

Background and aims Portopulmonary hypertension (POPH) hampers survival of patients with cirrhosis and portal hypertension and may preclude liver transplantation (LT). Management of such patients with oral pulmonary vasoactive drugs (PVD) has not been standardized. Our aim was to assess the efficacy and safety of oral PVD for management of POPH. Methods All patients treated by oral PVD (bosentan, ambrisentan, sildenafil, tadalafil) for POPH were retrospectively studied. Significant response was defined for the patients who reached the following LT eligibility criteria: mean pulmonary artery pressure (MPAP) −5 . Results 20 patients were followed for 38 (19–57) months. Oral PVD improved MPAP (−8 [−19, +2] mmHg), PVR (−201 [–344, –68] dyn s cm −5 ) and 6-min walk distance (+52 [−51, +112] m). Fifty-three percent of evaluable patients reached eligibility to LT criteria, of whom 5 were transplanted. Baseline MPAP > 51 mmHg and/or PVR > 536 dyn s cm −5 predicted non response to treatment. Five-years survival was 53%. No worsening of cirrhosis or serious adverse effect was recorded. Conclusion Oral pulmonary vasoactive drugs are safe in cirrhotic patients with POPH. These treatments improved hemodynamic conditions allowing patients access to liver transplantation eligibility.

AKOS (Traite de Medecine) - Epreuve corrigee par l'auteur. Disponible en ligne depuis le 16/05/2017

Introduction et but de l’etude Les personnes atteintes de cirrhose sont les plus a risque de developper un carcinome hepatocellulaire (CHC), cancer au pronostic sombre. Le foie joue un role central dans le metabolisme des nutriments, en particulier des lipides. Pourtant, les liens entre consommation de lipides, metabolisme lipidique et risque de CHC en cas de cirrhose ne sont pas encore bien definis. L’objectif de ce travail etait d’etudier le profil en acides gras (AG) de la membrane erythrocytaire (reflet des apports alimentaires et du metabolisme) chez des personnes atteintes de cirrhose, selon la presence ou non d’un CHC. Materiel et methodes L’etude multicentrique CiRCE a inclus 1178 patients cirrhotiques sans CHC a l’inclusion (temoins) ou avec CHC histologiquement confirme (cas). La composition en AG de la membrane des erythrocytes a ete determinee par chromatographie en phase gazeuse a haute performance chez 349 cas et 550 temoins. L’association entre le risque de CHC et la concentration de differents AG decoupee en tertiles a ete evaluee par regression logistique multivariee. Resultats et analyse statistique Les cas etaient plus âges que les temoins [âge median : 64,2 versus 58,9 ans, (p = 0,04)] et plus souvent des hommes. Une association positive etait mise en evidence entre le risque de CHC et la concentration en acide linoleique (18 :2 n–6) [Odds Ratio (OR) = 2,22 [Intervalle de Confiance (IC) a 95 % 1,43–3,43] (p Conclusion Les profils en AG des membranes erythrocytaires etaient differents selon la presence ou non de CHC chez les personnes atteintes de cirrhose. Les activites enzymatiques semblaient egalement perturbees. Ces resultats et les hypotheses mecanistiques devront etre confirmes dans une etude prospective.

Resume Le domaine des surcharges hereditaires en fer a connu, dans la periode recente, de profondes evolutions liees a de grandes avancees de la biologie et de la genetique moleculaires. Il recouvre desormais de nombreuses entites pathologiques. Les mecanismes sous-tendant le developpement de la surcharge viscerale en fer ainsi que la toxicite du fer sont de mieux en mieux compris. Le diagnostic de ces pathologies repose sur une approche non invasive dans laquelle la biologie tient un role majeur. Le traitement de ces affections, longtemps base sur la simple soustraction sanguine, s’enrichit desormais d’une possibilite de chelation medicamenteuse orale et surtout de perspectives therapeutiques innovantes directement issues des progres dans la comprehension moleculaire de ces maladies.

Incidental liver nodules are more and more frequently encountered because of increasing sensitivity of recent imaging techniques. The identification of biliary cyst or hemangioma is usually easy. In other cases, the etiological diagnosis relies on careful radiological analysis of the pattern of the arterial phase enhancement following contrast medium injection. When there is no early arterial enhancement, a liver biopsy is usually indicated to establish the diagnosis. A strong arterial contrast enhancement pattern is indicative of hepatocellular tumor, benign or malignant. In this situation, it is crucial to establish if there is underlying liver fibrosis. In case of cirrhosis, the diagnosis of hepatocellular carcinoma is the most probable. If the non tumorous liver is normal, focal nodular hyperplasia and hepatocellular adenoma should be differentiated. The distinction between these two tumors is important because only hepatic adenoma carries a significant risk of complications (bleeding or hepatocellular carcinoma) leading to surgical resection of lesions that do not regress after steroid withdrawal. Contrast enhanced MRI and contrast ultrasound are most useful tools for the diagnosis of nodular regenerative hyperplasia but liver biopsy can be necessary in atypical forms. In recent years, the understanding of molecular mechanisms associated with adenoma occurrence allowed for the proposal of a new classification already of practical interest in the management of patients.

Resume La caracterisation d’une masse abdominale en imagerie pose regulierement probleme aux radiologues et aux cliniciens. Nous rapportons le cas d’une masse peripancreatique atypique suspecte de neoplasie en imagerie dont la nature exacte n’a pu etre precisee qu’apres examen anatomopathologique d’une ponction echoendoscopique. Le diagnostic de tuberculose abdominale est difficile en l’absence d’atteinte pulmonaire associee. Le diagnostic de certitude ne peut etre obtenu que par examen anatomopathologique. Le plus souvent, il s’agit d’une anatomopathologie realisee sur piece operatoire apres chirurgie d’exerese de la masse. La biopsie sous echoendoscopie a permis, chez notre patient, de preciser le diagnostic de cette masse pseudotumorale et d’eviter une chirurgie complexe et mutilante. Dans le cas de tuberculose pancreatique ou peripancreatique, les biopsies permettent d’eviter une chirurgie inutile.

To identify risk factors associated with survival in patients retransplanted for hepatitis C virus (HCV) recurrence and to apply a survival score to this population.We retrospectively identified 108 patients retransplanted for HCV recurrence in eight European liver transplantation centers (seven in France, one in Spain). Data collection comprised clinical and laboratory variables, including virological and antiviral treatment data. We then analyzed the factors associated with survival in this population. A recently published score that predicts survival in retransplantation in patients with hepatitis C was applied. Because there are currently no uniform recommendations regarding selection of the best candidates for retransplantation in this setting, we also described the clinical characteristics of 164 patients not retransplanted, with F3, F4, or fibrosing cholestatic hepatitis (FCH) post-first graft presenting with hepatic decompensation.Overall retransplantation patient survival rates were 55%, 47%, and 43% at 3, 5, and 10 years, respectively. Patients who were retransplanted for advanced cirrhosis had survival rates of 59%, 52%, and 49% at 3, 5, and 10 years, while those retransplanted for FCH had survival rates of 34%, 29%, and 11%, respectively. Under multivariate analysis, and adjusting for the center effect and the occurrence of FCH, factors associated with better survival after retransplantation were: negative HCV viremia before retransplantation, antiviral therapy after retransplantation, non-genotype 1, a Model for End-stage Liver Disease (MELD) score25 when replaced on the waiting list, and a retransplantation donor age60 years. Although the numbers were small, in the context of the new antivirals era, we showed that outcomes in patients who underwent retransplantation with undetectable HCV viremia did not depend on donor age and MELD score. The Andrés score was applied to 102 patients for whom all score variables were available, producing a mean score of 43.4 (SD = 6.6). Survival rates after the date of the first decompensation post-first liver transplantation (LT1) in the liver retransplantation (reLT) group (94 patients decompensated) at 3, 5, and 10 years were 62%, 59%, and 51%, respectively, among 78 retransplanted individuals with advanced cirrhosis, and 42%, 32%, and 16% among 16 retransplanted individuals with FCH. In the non-reLT group with hepatic decompensation, survival rates were 27%, 18%, and 9% at 3, 5, and 10 years, respectively (P0.0001). Compared with non-retransplanted patients, retransplanted patients were younger at LT1 (mean age 48 ± 8 years compared to 53 ± 9 years in the no reLT group, P0.0001), less likely to have human immunodeficiency virus (HIV) co-infection (4% vs 14% among no reLT patients, P = 0.005), more likely to have received corticosteroid bolus therapy after LT1 (25% in reLT vs 12% in the no reLT group, P = 0.01), and more likely to have presented with sustained virological response (SVR) after the first transplantation (20% in the reLT group vs 7% in the no reLT group, P = 0.028).Antiviral therapy before and after retransplantation had a substantial impact on survival in the context of retransplantation for HCV recurrence, and with the new direct-acting antivirals now available, outcomes should be even better in the future.

International audience; Background & aims - In patients with cirrhosis, cystatin C (CystC) based equations may be more accurate indicators of glomerular filtration rate (GFR) than creatinine (Pcr) based equations. Renal function before liver transplantation (LT) is thought to impact survival after LT. We aimed at assessing pretransplant creatinine and CystC based equations with respect to their predictive value on long-term survival after LT. Methods - From 2001 to 2011, CystC was determined at pre-LT evaluation in 682 patients together with GFR assessed using MDRD-4, MDRD-6, CKD-EPI-cystatin C, CKD-EPI-creatinine and CKD-EPI-creatinine-cystatin C equations. Patients were classified according to the Kidney Disease Outcomes Quality Initiative classification (KDOQI). Results - Median age at LT was 55 [49-60] years with a median MELD score of 13.5 [8.3-19.2] and a median post-transplant follow-up of 60 [26-89] months. Using CKD-EPI Cystatin C and the KDOQI classification, 21.1% of patients were stage 1, 43.1% stage 2, 29.1% stage 3 and 6.5% stage 4. Kaplan-Meier survival estimates were significantly different between KDOQI stages when determined using the CKD-EPI-CystatinC equation. This was not the case when using the other equations. At multivariate analysis, GFR and KDOQI estimated using the CKD-EPI-CystatinC equation were significantly associated with death (HR: 0.992; CI95%: 0.986-0.999 and 1.24; CI95%: 1.02-1.50 respectively). When assessed using the MDRD-4, MDRD-6, CKD-EPI-Creatinine-CystatinC and CKD-EPI-Creatinine equations GFR was not significantly associated with death. Conclusions - Estimated pre-LT renal function is predictive of post-LT survival only when assessed using the CKD-EPI cystatin C equation. This supports the use of Cystatine C and of its related equation for the assessment of renal function before liver transplantation.

Introduction et but de l’etude La denutrition aggrave le pronostic de la cirrhose. Nous manquons d’outils permettant d’evaluer la masse musculaire. La mesure de la masse musculaire par scanner centre sur la troisieme vertebre lombaire necessite un logiciel specifique, du temps et une expertise radiologique. L’objectif principal etait d’evaluer si les mesures du diametre axial (DAMP) et transversal du psoas (DTMP) indexes a la taille (DAMPI, DTMPI) etaient des facteurs independants de mortalite dans une population de cirrhotiques inscrits sur liste d’attente de transplantation hepatique. Materiel et methodes Etude observationnelle monocentrique retrospective. Criteres d’inclusion : patients inscrits consecutivement sur liste de transplantation hepatique entre le 01/01/2007 au 31/12/2012 ; cirrhose isolee ; scanner abdominal disponible dans les 3 mois encadrant l’inscription. Critere principal de jugement : survenue du deces ou sortie de liste pour aggravation. Le DAMP, diametre anteroposterieur le plus long, et le DTMP, perpendiculaire au DAMP, ont ete mesures sur une coupe TDM passant par l’ombilic, par un operateur non entraine, et par un radiologue (n = 50), et rapportes a la taille pour calculer le DAMPI et le DTMPI (exprimes en millimetres par metre). La reproductibilite entre les deux operateurs a ete mesuree par test de correlation kappa. Les analyses uni- et multivariees ont ete realisees par regression logistique selon modele de Cox. Les seuils de DAMPI et de DTMPI associes a la mortalite ont ete definis au moyen d’une courbe ROC. Les courbes de survie selon la methode de Kaplan Meier ont ete comparees avec le Log-Rank test. Resultats Trois cent neuf patients cirrhotiques inscrits sur liste d’attente de transplantation hepatique ont ete inclus : moyenne ± ecart-type (ET) : 56 ± 1 ans, 87 % hommes, IMC : 26,8 ± 0,3 kg/m2, 70 % atteints de cirrhose alcoolique, score Model for End-stage Liver Disease (MELD) 18 ± 2. Le suivi median a ete de 7,1 ± 0,4 mois : 72 % de transplantations hepatiques, 8 % de deces, 20 % de sortie de liste. Les DTMPI et DAMPI moyens etaient respectivement de 16,1 ± 0,8 et 22,5 ± 0,7 mm/m. En analyse univariee, le DTMPI etait facteur predictif de mortalite sur liste (hazard ratio [HR] = 0,84 ; intervalle de confiance [IC] a 95 % : [0,78–0,89], p Conclusion Le DTMPI (= DTMP (exprime en millimetres)/taille (exprimee en metres)) est predictif de mortalite chez le patient cirrhotique inscrit sur liste de transplantation hepatique. C’est une mesure simple, reproductible, et faisable sans expertise radiologique. De futurs essais cliniques devront demontrer si une intervention nutritionnelle precoce chez les patients cirrhotiques avec DTMPI bas pourrait ameliorer leur pronostic.

International audience; ObjectivesDespite improvements in patient management and extensive use of therapeutic drug monitoring (TDM), the rate of acute cellular rejection (ACR) remains high in patients treated with tacrolimus (TAC). Moreover, some patients experienced ACR while their whole-blood (WB) concentrations were maintained within the therapeutic range meaning that TDM in WB misrepresents the drug effect. Thus, monitoring TAC directly inside of its effect compartment (intracellular concentrations) or monitoring directly the inhibitory effect on the target protein (calcineurin activity) could be more relevant. The aim of the present study was to explore, in 10 de novo liver transplant recipients, the relationship between TAC whole-blood concentrations, TAC intracellular concentrations and TAC-induced intracellular calcineurin inhibition at day 1 and day 7 after treatment initiation.Design and methodsProspective monocentric observational pharmacokinetic (WB and intracellular concentrations)–pharmacodynamic (calcineurin activity) study.ResultsFull intracellular TAC pharmacokinetic as well as calcineurin activity steady-state profiles is presented in the study. The main result of this study is the lack of relationship between TAC pharmacokinetics (WB and leukocytes) and calcineurin activity in leukocytes at day 1 and day 7 after the graft implantation.ConclusionsDrug monitoring of TAC intracellular concentrations and determination of the calcineurin activity are among future potential biomarkers of acute rejection in transplant recipients. A better knowledge of the relationship between TAC whole blood and intracellular concentrations and calcineurin activity appears necessary before planning clinical trials to evaluate their potential interest as predictive biomarkers.

International audience; Background - The treatment of HFE-related hemochromatosis, one of the most common genetic diseases, is based on phlebotomies whose tolerance is evaluated by regular monitoring of hemoglobin. Using a portable hemoglobinometer (PH) could provide an easy and fast determination of hemoglobin. Therefore, the aim of the present study was to compare, in hemochromatosis patients treated by bloodletting, the hemoglobin concentrations as assayed, on capillary blood, by a PH device and, on venous blood, by a cell counter (CC) device. Methods - For a total period of 12 weeks duration, all patients undergoing phlebotomies in the same hospital outpatient unit had hemoglobin determinations both by the HemoCue and by the laboratory's DxH 800 Coulter. To evaluate the sensitivity and specificity of the HemoCue, patients were classified as presenting or not anemia as defined by hemoglobin level below 11 g/dl. Results - Measurements of hemoglobin were performed in 122 patients. The sensitivity and specificity of PH compared to CC were 100 and 98.1%, respectively. Capillary hemoglobin by PH slightly underestimated venous hemoglobin by CC. The Pearson's correlation coefficient between PH and CC was 0.80 (P

Defects in human hemochromatosis protein (HFE) cause iron overload due to reduced hepatic hepcidin secretion. Liver transplantation (LT) is a key treatment for potential complications from HFE-related hereditary hemochromatosis (HH). This study evaluated hepcidin secretion and iron burden after LT to elucidate HH pathophysiology. Patients (n=18) homozygous for the p.Cys282Tyr mutation in the HFE gene underwent LT between 1999 and 2008. Serum iron, serum hepcidin, and hepatic iron concentrations were determined before LT and at the end of follow-up (median 57 months). Mortality and causes of death were determined. Survival was compared to that of the overall patient population that received LT. Before LT, serum hepcidin levels were low (0.54 ± 2.5 nmol/L; normal range: 4-30 nmol/L). After LT, 11 patients had iron evaluations; none received iron depletion therapy; all had normal transferrin saturation. The mean serum ferritin was 185 (± 99) μg/L. Magnetic resonance imaging showed that iron overload was absent in nine patients, mild in one patient with metabolic syndrome, and high (180 μmol/g) in one patient with hereditary spherocytosis discovered after LT. At the end of follow-up, serum hepcidin was normal in 10 patients (11.12 ± 7.6 nmol/L; P0.05) and low in one patient with iron deficiency anemia. Survival was 83% and 67% at 1 and 5 years, respectively. Survival was similar for patients with HH and patients that received LT for other causes.In HH, LT normalized hepcidin secretion and prevented recurrence of hepatic iron overload. Survival was similar to that of patients who received LTs for other liver diseases.

Portal vein tumor thrombosis (PVTT) is a common complication of hepatocellular carcinoma (HCC) and has a negative impact on prognosis. This characteristic feature led to the rationale of the present trial designed to assess the efficacy and the safety of yttrium-90 glass-microsphere treatment for advanced-stage lobar HCC with ipsilateral PVTT. 18 patients with unresectable lobar HCC and ipsilateral PVTT were treated in our institution with90Y-microS radioembolization. Patients were evaluated every 3 to 6 months for response, survival, and toxicity. Mean follow-up was 13.0 months (2.2–50.6). Outcomes were: complete response (n=2), partial response (n=13), stable disease (n=1), and progressive disease (n=2) giving a disease control rate of 88.9%. Four patients were downstaged. Treating lobar hepatocellular carcinoma with ipsilateral portal vein thrombosis with yttrium-90 glass-microsphere radioembolization is safe and efficacious. Further clinical trials are warranted to confirm these results and to compare90Y-microS with sorafenib, taking into account not only survival but also the possibility of secondary surgery for putative curative intention after downstaging.

Goals and Background: We evaluated the efficacy and medium-term outcomes of transcatheter embolization to control massive bleeding from gastroduodenal ulcers after failed endoscopic treatment in high-operative-risk patients. Study: Retrospective study of 35 consecutive emergency embolization procedures in hemodynamically unstable patients (24 men, 11 women, mean age 71 ± 11.6 y) referred from 1999 to 2006 for selective angiography after failed endoscopic treatment. Mean follow-up was 27 months. Results: Endovascular treatment was feasible in 33 patients and consistently stopped the bleeding. "Sandwich" coiling of the gastroduodenal artery was performed in 11 patients and superselective occlusion of the terminal feeding artery with glue, coils, or gelatine particles in 22 patients. Early rebleeding occurred in 6 patients and was managed successfully using endoscopy (n = 2), reembolization (n = 1), or surgery (n = 3). No major complications related to catheterization occurred. Seven patients died within 30 days of embolization and 3 died later during the follow-up, but none of the deaths were due to rebleeding. No late bleeding recurrences were reported. Conclusions: Selective angiographic embolization is safe and effective for controlling life-threatening bleeding from gastroduodenal ulcers, usually obviating the need for emergency surgery in critically ill patients, whose immediate survival depends on their underlying conditions.

The aim of this study was to calculate the risk of metachronous colorectal cancers, to specify their characteristics and potential risk factors in a well-defined French population over a 27-year period.The 10,801 patients who had colorectal cancers totalled 61,879 person-years of follow-up. The actuarial method was used to obtain crude metachronous colorectal cancer rates. Standardised incidence ratios (SIRs) were calculated.The cumulative rate of metachronous colorectal cancer was 1.8% at 5 years, 3.4% at 10 years and 7.2% at 20 years. The incidence of metachronous colorectal cancer following a first colorectal cancer was higher than expected (SIR: 1.5 [1.3-1.7] p0.001). It remained greater throughout the study period, significantly only between the first and the fifth years following diagnosis (SIR: 1.9 [1.6-2.3] p0.010). As compared to solitary cancers, metachronous cancers were diagnosed at earlier stages (23.5% versus 40.9% were stage I, p0.001). None of the personal and tumour characteristics were predicting factors for the development of metachronous colorectal cancer.Patients with colorectal cancer are at greater risk of developing a metachronous colorectal cancer. Among them, no predicting factors for the development of metachronous tumours were found. Thus lifelong colonoscopic surveillance is needed.

P890 SPECIFIC PHENOTYPE AND GENE EXPRESSION PROFILES OF COMBINED LIVER AND KIDNEY TRANSPLANTED PATIENTS IN PERIPHERAL BLOOD MONONUCLEAR CELLS E. Dumontet, R. Danger, P. Vagefi, M.-C. Londono, A. Pallier, J.J. Lozano, M. Giral, N. Degauque, M. Martinez-Llordella, M. Latournerie, K. Boudjema, J. Dulong, K. Tarte, J.-P. Soulillou, A. Sanchez-Fueyo, S. Feng, S. Brouard, S. Conchon. Institut National de la Sante et de la Recherche Medicale, INSERM U 1064, Centre Hospitalier Universitaire Hotel-Dieu, Universite de Nantes, Nantes, France; King’s College London – Institute of Liver Studies, King’s College Hospital, London, United Kingdom; Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Liver Unit and Bioinformatic Platform, Hospital Clinic Barcelona, Barcelona, Spain; Centre Hospitalier Universitaire Pontchaillou, EFS Bretagne, Institut National de la Sante et de la Recherche Medicale, INSERM U 917, Rennes, France; Department of Surgery-Division of Transplantation, University of California, San Francisco, CA, United States E-mail: erwan.dumontet@etu.univ-nantes.fr

International audience; AIM: To determine the evolution of transient elastography (TE) in patients with alcoholic liver disease according to alcohol cessation or continuation. METHODS: We retrospectively selected in our local database all patients who had two TE between June 2005 and November 2010 with chronic alcohol excessive consumption and excluded those with associated cause of liver disease. TE was performed at least one week apart by senior operator. TE examinations with less than ten successful measures or with an interquartile range above 30% were excluded. We retrospectively reviewed file of all patients to include only patient followed up by trained addictologist and for which definite information on alcohol consumption was available. Concomitant biological parameters [aspartate amino transferase (AST), alanine amino transferase and gamma-glutamyl transpeptidase (GGT)] within 4 wk of initial and final TE were recorded. Putative fibrosis score according to initial and final TE were determined with available cut-off for alcoholic liver disease and hepatitis C. Initial and final putative fibrosis score were compared according to alcohol consumption during follow-up. RESULTS: During the study period 572 patients had TE examination for alcoholic liver disease and 79 of them had at least two examinations. Thirty-seven patients met our criteria with a median follow-up of 32.5 wk. At the end of the study, 13 (35%) were abstinent, and 24 (65%) relapsers. Eight patients had liver biopsy during follow-up. TE decreased significantly during follow-up in 85% of abstinent patients [median (range): -4.9 (-6.1,-1.9)], leading to a modification of the putative fibrosis stage in 28%-71% of patient according to different cut-off value. In relapsers TE increased in 45% and decreased in 54% of patient. There was no statistical difference between initial and final TE in relapsers. In the overall population, using 22.6 kPa as cut-off for cirrhosis, 4 patients had cirrhosis at initial TE and 3 patients had cirrhosis at final TE. Using 19.5 kPa as cut-off for cirrhosis, 7 patients had cirrhosis at initial TE and 5 patients had cirrhosis at final TE. Using 12.5 kPa as cut-off for cirrhosis, 16 patients had cirrhosis at initial TE and 15 patients had cirrhosis at final TE. Evolution of biological data was in accordance with the relapse or abstinent status: abstinence ratio (duration of abstinence/duration follow-up) was correlated with AST ratio (r = -0.465, P = 0.007) and GGT ratio (r = -0.662, P < 0.0001). GGT was correlated with initial (r = 0.488, P = 0.002) and final TE (r = 0.49, P < 0.005). Final TE was correlated with AST (r = 0.362, P < 0.05). Correlation between TE ratio and AST ratio (r = 0.44, P = 0.01) revealed that TE varied proportionally to AST for all patients irrespective of their alcohol status. The same relationship was observed between TE ratio and GGT ratio (r = 0.65, P < 0.0001). Evolution of TE was significantly correlated with the ratio of time of abstinence to observation time (r = -0.387, P = 0.016) and the evolution of liver enzymes. CONCLUSION: TE significantly decreased with abstinence. Results of TE in alcoholic liver disease cannot be interpreted without taking into account alcohol consumption and liver enzymes.